Cell and Gene Therapy: Delivering the Product

George Goldberger spent more than 20 years helping to build the leading cell and gene manufacturing contract development organization, PCT (now part of Hitachi as Hitachi Chemical Advanced Therapeutics Solutions). Serving as PCT’s Chief Financial Officer and Business Officer and then Vice President, Business Development, he worked with cell and gene therapy companies from around the world looking for contract manufacturing and related development services. Seeing a growing need for strategic advice on how to turn cell and gene therapy products into a commercial reality-to bridge the gap between “excellent science and commercial realization”-he established Cell One Partners in 2018 to support clients in all aspects of the commercialization pathway.

Pharm Exec caught up with Goldberger to discuss the issues that new and emerging cell and gene therapy companies face on the road to commercialization, and how he is positioning Cell One Partners as their “indispensable” strategic partner.

What are the biggest challenges that new companies in cell and gene therapy face now?

George Goldberger

George Goldberger: In a very general sense, I think it’s about delivery of the product. Something may work in a laboratory and maybe even with a single-digit number of patients, but it needs to be engineered so it can work on a large scale, for hundreds, maybe thousands, maybe tens of thousands of patients. Manufacturing and consistent delivery are what we find to be the biggest challenges in a commercial setting.

These challenges are much bigger than in a clinical trial setting. If we look at a clinical trial setting, usually there's some extraction of blood or blood-related product from a patient that goes to a manufacturing facility, where it is engineered and then returned for infusion. It's a two-way trip, particularly for autologous therapy. If something doesn’t go quite right in that process, the patient doesn't get the infusion and that's the end of that. But once a product gets approved, the process must work perfectly because if it doesn't, that means some patients don’t get the treatment, and, potentially, don’t get the cure. And that's another order of magnitude in complexity.

A combination of science and very sophisticated manufacturing needs to occur in concert, and it needs to occur from the perspective of the respective patients. Manufacturing is expensive, it is sophisticated, and companies need to think through how the product goes from the patient to the manufacturing facility and back to the bedside. Virtually all the clients that we have, and many are developing companies, are saying, “How are we actually going to do that?”

What trends are you seeing among cell and gene therapy companies regarding manufacturing?

Many of these are early-stage developmental companies may have had early success with a limited amount of clinical trial activity. They may have done an early-phase trial, sometimes affiliated with an academic or research institution. They may have treated half a dozen or a dozen patients. Now they’re moving to the next stage of treatment, which could involve several dozen patients, maybe even a couple of hundred. Usually, the academic institutions don't have the capacity, dedication, or even the initiative or willingness to undertake a higher level of manufacturing or cell engineering, as the focus at these institutions is typically on research and development. That's the point at which a cell therapy company will think about contracting for the remainder of their manufacturing needs. And the key decision points are: who do you contract with, what do you contract for, what is your level of confidence with your own product being manufactured by someone else, and is this all realistic and cost effective in the context of existing modalities of treatment? At some point, you're going to have to ask the question, “Do I continue to contract out- including through commercial delivery -or do I begin to build my own, and if so, when and with what scope?”

Correlated to this-and the two are interdependent-these early-stage products are typically manipulated in a clean room with operators and the work is essentially manual. If you have operators manipulating cell products, one-on-one for patients, it's very labor intensive. Such level of labor intensity is not naturally compatible with a product that you deliver on a commercial scale. At some point, you start looking at automation to take the personnel out of it and reduce the error rate and improve product outcome consistency. That goes in conjunction with the manufacturing setting. Companies will say, “If we’re going to automate and we’re going to manufacture in high numbers, do we do this in-house, or do we bring a partner as contract manufacturer?” This is the sweet spot on which Cell One Partners tends to advise. These are multi-million-dollar decisions.

What things would you say companies are doing right?

“Right” is if they think about the whole process all the way to commercialization. They take the point of view of the board of directors, who have the ultimate fiduciary responsibility with the funds the company is spending. They ask, “How are we going to get a return and when?” A goal could be that there's a liquidity event, meaning that you sell the product or sell the know-how at some point before commercialization. That's an entirely reasonable goal. Or the goal could be that your product is so unique, so powerful, and you have adequate financing, that you take it all the way to commercialization. That's what some companies are doing right. Companies that are not doing it right are, in general, are companies that just want to get through the next clinical trial, then worry about what to do later. Some companies are compelled to do that because they don't have financial resources to go further. But then you are compelled to ask the question: “Is what you're doing the best possible pathway to generating value?”

When a company comes to you, what kind of experience can they expect?

I've been able to assemble a team of nearly 30 professionals who have broad expertise in the multi-discipline aspects of cell and gene therapy development. One reality of this industry is that about half the development costs are associated with developing customized quality systems to ensure that the product that you manufacture is compatible with current Good Manufacturing Practices (cGMP). We’re able to offer the full range of services either as advisors or on a contract basis and thus become an extension of the clients’ management team. With a couple of our clients, we are in fact an extension of their advisory board or technical advisory board; we are the interface point between the companies and the contract manufacturers, or between the companies and developmental facilities. In effect, we complement a company, depending on its stage of development.

Where are your clients coming from, geographically?

While I am based in New York, many of the other Cell One Partner associates are based throughout the country and in Europe and Asia. About half the action in the industry is in North America and a quarter is in Europe, and probably 15 to 20% is in Asia. I think our client base is somewhat representative of that. We have some clients from Europe; we have some clients from the United States and Canada. We have had intensive inquiries from Asia. Those countries, particularly Japan, are looking at this industry globally, and saying, “This is the next generation of treatment in medicine. What can we learn from the rest of the world that could be applicable in Japan, or applicable in Japan by exporting to the rest of the world?” We're getting those kinds of inquiries, including very broad strategic inquiries.

What's your vision for Cell One Partners going forward?

The team can provide the best advice to companies – the best of the best - and a level of comfort to boards of directors that ensures their situation has been considered from different angles. I would like us to become an indispensable partner to companies that are looking to develop cell and gene therapies- an indispensable stopover on the clinical development pathway.

https://www.cellonepartners.com/